The incidence of obesity is increasing throughout the industrialized world and is a major public health concern. Some studies have shown a paradoxical protective effect of moderate obesity on outcome after percutaneous coronary intervention (PCI). The association between bleeding, body mass, and outcome is not well established and formed the basis for the present study, which examined major bleeding rates and mortality after PCI in British Columbia during a 6-year period. We identified 38,346 consecutive patients from the British Columbia Cardiac Registry who underwent PCI from 1999 to 2005. Data were cross-referenced to determine outcomes at 30 days and 1 year. Information about bleeding after PCI was obtained by cross-referencing the British Columbia Cardiac Registry with the Central Transfusion Registry. Baseline patient characteristics were compared among body mass index (BMI) categories. A clear bimodal (U-shaped) relation was seen between BMI and mortality. BMI was a potent independent predictor of mortality, particularly evident in the underweight (BMI <18.5 kg/m(2); odds ratio [OR] 1.98, 95% confidence interval [CI] 1.6 to 2.5, p <0.0001) and morbidly obese (> or =40 kg/m(2); OR 1.61, 95% CI 1.28 to 2.08, p <0.0001) groups. Periprocedural transfusion was also associated with adverse outcome (OR 2.86, 95% CI 2.52 to 3.25, p <0.0001). Transfusion adopted the same bimodal distribution across the entire cohort. Emergent PCI and femoral access were procedural factors associated with outcome. In conclusion, major bleeding conferred an adverse long-term prognosis after PCI. Identifying demographic and procedural factors that increase risk will facilitate more accurate risk scoring of patients undergoing PCI and allow targeted bleeding-avoidance strategies. Body mass and female gender identified subgroups at much higher risk of bleeding after PCI, an observation that merits further study.